Physical Activity Reduces Colorectal Cancer Morbidity and Mortality

NEW YORK – Moderate exercise can confer a measurable survival advantage in patients who have undergone treatment for colorectal cancer, said Dr. Jeffrey Meyerhardt at an international conference sponsored by the Society for Integrative Oncology.

"Published data are showing a major decrease in morbidity and mortality in patients who exercise. These are changes in actual cancer outcomes, not just quality of life measures," said Dr. Meyerhardt of the department of medical oncology, Dana-Farber Cancer Institute, Boston.

"My research really came out of patients’ questions. They wanted to know, ‘What should I be eating? Should I exercise? What else can I do to improve my chances?’ We wanted to help them live longer and live better."

Emerging data indicate that physical activity, avoidance of the typical meat-heavy Western diet patterns, maintenance of body mass index under 35 kg/m2, higher levels of vitamin D, and regular use of aspirin or other anti-inflammatory compounds reduces the risk of recurrence in colorectal cancer (CRC), Dr. Meyerhardt said during his keynote presentation.

An Australian cohort study of 526 colorectal cancer patients showed that the probability of surviving for 10 years post-diagnosis was 73% for the patients who exercised regularly prior to the cancer diagnosis, versus 54% among those who did not exercise (Gut 2006;55:62-7). The investigators noted that percent of body fat and the waist circumference were both inversely correlated with survival.

Dr. Meyerhardt and his group published an analysis of data from a National Cancer Institute–sponsored study called CALGB 89803 that involved 1,264 patients with stage II colon cancer, randomized to treatment with 5-fluorouracil and leucovorin with or without irinotecan following surgical resection.

The study was designed to assess the impact of the drug regimens on overall and disease-free survival, and found no significant differences between the two (J. Clin. Oncol. 2007;25:3456-61). However, there were substantial survival differences based on level of post-diagnosis physical activity, said Dr. Meyerhardt.

He and his colleagues stratified the study participants according to their self-reported activity levels, using the "met-hour" (metabolic equivalent task hour) as a unit of measure. For example, sitting still was defined as 1 met and slow walking was defined as 3 mets. Other activities were assigned met values according to their strenuousness. Met-hours represent the aggregate amount of time per week that a subject spent in metabolically significant activity.

The hazard ratio of recurrence or death was reduced by 49% among people who regularly had between 18 and 26 met-hours of activity per week, compared to those who had fewer than 3 met-hours per week (J. Clin. Oncol. 2006;24:3535-41). Dr. Meyerhardt said that an hour-long walk at a brisk pace of 3-4 miles per hour, three to four times per week, would put someone in the risk-reducing range.

He acknowledged that this analysis has limits in that it was based on self-reporting. Also, people who are able to exercise for 18 or more hours per week after chemotherapy and surgery for colorectal cancer are highly functioning, with good overall health status, which in and of itself would confer a survival advantage.

Data from other studies have also shown that higher activity levels predict better outcomes following colorectal cancer diagnosis. For example, the Nurses’ Health Study showed that post-diagnosis activity levels are predictive of survival. Among the women who had more than 18 met-hours of activity per week, roughly 90% were still alive 10 years after diagnosis, versus 67% of those who had less than 3 met hours per week, and 75% of those who got between 3 and 18 met-hours/week (J. Clin. Oncol. 2006;24:3527-34). In this data set, the prediagnosis activity levels were not predictive of survival, after researchers adjusted for other health status variables.

"It is not simply a matter of more active people getting less aggressive forms of cancer," said Dr. Meyerhardt. "There are statistically significant improvements in survival and reduced morbidity in patients with increased activity post-diagnosis and post-treatment."

The NHS data indicate that women who increased their activity levels post-diagnosis had about 50% reductions in hazard ratios for CRC-specific mortality and overall mortality, while those who decreased their physical activity had increases in their hazard ratios.

A soon-to-be published analysis of data from the Health Professionals Follow-Up Study, involving 51,500 male health care practitioners, showed a similar pattern of reduced overall and CRC-associated mortality among the men with the highest levels of post-diagnosis physical activity, said Dr. Meyerhardt.

He noted that these studies are observational, and a prospective study is needed to confirm their findings. The Colon Health and Life-Long Exercise Change (CHALLENGE) trial is such a study that is expected to be published in several years. An Australian-Canadian collaborative effort, this controlled study will look at the impact of direct, guided exercise training interventions on clinical outcomes in patients with high-risk stage II and III CRC following surgery and adjuvant chemotherapy.

It is not yet known how exercise affects CRC, and cancer in general. Dr. Meyerhardt believes that the potential benefits may be partially attributable to the ability of exercise to modulate insulin metabolism. He noted that elevated insulin and insulin-like growth factors are predictive of increased CRC morbidity and mortality, as is elevation of C-peptide, another marker of insulin resistance.

Insulin resistance and all the metabolic changes that go with it may be a common factor between obesity and colorectal cancer. While not all studies have shown a direct correlation, there are data to suggest that a BMI over 30 kg/m2confers a 25% increase in risk of colorectal cancer recurrence and death.

‘With the rising incidence of obesity in the U.S., we are seeing more obese colorectal cancer patients," said Dr. Meyerhardt. "It used to be that only about 5% of colorectal cancer patients were obese. Now it’s roughly 10%."

He concluded that while there are many unanswered questions, there’s little harm and much potential good in recommending moderate regular physical activity for patients who have undergone surgery and adjuvant chemotherapy for colorectal cancer. Benefits increase if patients can shift toward a low-fat diet rich in vegetables and low in red meat and processed foods, he added.

NEW YORK – Moderate exercise can confer a measurable survival advantage in patients who have undergone treatment for colorectal cancer, said Dr. Jeffrey Meyerhardt at an international conference sponsored by the Society for Integrative Oncology.

"Published data are showing a major decrease in morbidity and mortality in patients who exercise. These are changes in actual cancer outcomes, not just quality of life measures," said Dr. Meyerhardt of the department of medical oncology, Dana-Farber Cancer Institute, Boston.

"My research really came out of patients’ questions. They wanted to know, ‘What should I be eating? Should I exercise? What else can I do to improve my chances?’ We wanted to help them live longer and live better."

Emerging data indicate that physical activity, avoidance of the typical meat-heavy Western diet patterns, maintenance of body mass index under 35 kg/m2, higher levels of vitamin D, and regular use of aspirin or other anti-inflammatory compounds reduces the risk of recurrence in colorectal cancer (CRC), Dr. Meyerhardt said during his keynote presentation.

An Australian cohort study of 526 colorectal cancer patients showed that the probability of surviving for 10 years post-diagnosis was 73% for the patients who exercised regularly prior to the cancer diagnosis, versus 54% among those who did not exercise (Gut 2006;55:62-7). The investigators noted that percent of body fat and the waist circumference were both inversely correlated with survival.

Dr. Meyerhardt and his group published an analysis of data from a National Cancer Institute–sponsored study called CALGB 89803 that involved 1,264 patients with stage II colon cancer, randomized to treatment with 5-fluorouracil and leucovorin with or without irinotecan following surgical resection.

The study was designed to assess the impact of the drug regimens on overall and disease-free survival, and found no significant differences between the two (J. Clin. Oncol. 2007;25:3456-61). However, there were substantial survival differences based on level of post-diagnosis physical activity, said Dr. Meyerhardt.

He and his colleagues stratified the study participants according to their self-reported activity levels, using the "met-hour" (metabolic equivalent task hour) as a unit of measure. For example, sitting still was defined as 1 met and slow walking was defined as 3 mets. Other activities were assigned met values according to their strenuousness. Met-hours represent the aggregate amount of time per week that a subject spent in metabolically significant activity.

The hazard ratio of recurrence or death was reduced by 49% among people who regularly had between 18 and 26 met-hours of activity per week, compared to those who had fewer than 3 met-hours per week (J. Clin. Oncol. 2006;24:3535-41). Dr. Meyerhardt said that an hour-long walk at a brisk pace of 3-4 miles per hour, three to four times per week, would put someone in the risk-reducing range.

He acknowledged that this analysis has limits in that it was based on self-reporting. Also, people who are able to exercise for 18 or more hours per week after chemotherapy and surgery for colorectal cancer are highly functioning, with good overall health status, which in and of itself would confer a survival advantage.

Data from other studies have also shown that higher activity levels predict better outcomes following colorectal cancer diagnosis. For example, the Nurses’ Health Study showed that post-diagnosis activity levels are predictive of survival. Among the women who had more than 18 met-hours of activity per week, roughly 90% were still alive 10 years after diagnosis, versus 67% of those who had less than 3 met hours per week, and 75% of those who got between 3 and 18 met-hours/week (J. Clin. Oncol. 2006;24:3527-34). In this data set, the prediagnosis activity levels were not predictive of survival, after researchers adjusted for other health status variables.

"It is not simply a matter of more active people getting less aggressive forms of cancer," said Dr. Meyerhardt. "There are statistically significant improvements in survival and reduced morbidity in patients with increased activity post-diagnosis and post-treatment."

The NHS data indicate that women who increased their activity levels post-diagnosis had about 50% reductions in hazard ratios for CRC-specific mortality and overall mortality, while those who decreased their physical activity had increases in their hazard ratios.

A soon-to-be published analysis of data from the Health Professionals Follow-Up Study, involving 51,500 male health care practitioners, showed a similar pattern of reduced overall and CRC-associated mortality among the men with the highest levels of post-diagnosis physical activity, said Dr. Meyerhardt.

He noted that these studies are observational, and a prospective study is needed to confirm their findings. The Colon Health and Life-Long Exercise Change (CHALLENGE) trial is such a study that is expected to be published in several years. An Australian-Canadian collaborative effort, this controlled study will look at the impact of direct, guided exercise training interventions on clinical outcomes in patients with high-risk stage II and III CRC following surgery and adjuvant chemotherapy.

It is not yet known how exercise affects CRC, and cancer in general. Dr. Meyerhardt believes that the potential benefits may be partially attributable to the ability of exercise to modulate insulin metabolism. He noted that elevated insulin and insulin-like growth factors are predictive of increased CRC morbidity and mortality, as is elevation of C-peptide, another marker of insulin resistance.

Insulin resistance and all the metabolic changes that go with it may be a common factor between obesity and colorectal cancer. While not all studies have shown a direct correlation, there are data to suggest that a BMI over 30 kg/m2confers a 25% increase in risk of colorectal cancer recurrence and death.

‘With the rising incidence of obesity in the U.S., we are seeing more obese colorectal cancer patients," said Dr. Meyerhardt. "It used to be that only about 5% of colorectal cancer patients were obese. Now it’s roughly 10%."

He concluded that while there are many unanswered questions, there’s little harm and much potential good in recommending moderate regular physical activity for patients who have undergone surgery and adjuvant chemotherapy for colorectal cancer. Benefits increase if patients can shift toward a low-fat diet rich in vegetables and low in red meat and processed foods, he added.

NEW YORK – Moderate exercise can confer a measurable survival advantage in patients who have undergone treatment for colorectal cancer, said Dr. Jeffrey Meyerhardt at an international conference sponsored by the Society for Integrative Oncology.

"Published data are showing a major decrease in morbidity and mortality in patients who exercise. These are changes in actual cancer outcomes, not just quality of life measures," said Dr. Meyerhardt of the department of medical oncology, Dana-Farber Cancer Institute, Boston.

"My research really came out of patients’ questions. They wanted to know, ‘What should I be eating? Should I exercise? What else can I do to improve my chances?’ We wanted to help them live longer and live better."

Emerging data indicate that physical activity, avoidance of the typical meat-heavy Western diet patterns, maintenance of body mass index under 35 kg/m2, higher levels of vitamin D, and regular use of aspirin or other anti-inflammatory compounds reduces the risk of recurrence in colorectal cancer (CRC), Dr. Meyerhardt said during his keynote presentation.

An Australian cohort study of 526 colorectal cancer patients showed that the probability of surviving for 10 years post-diagnosis was 73% for the patients who exercised regularly prior to the cancer diagnosis, versus 54% among those who did not exercise (Gut 2006;55:62-7). The investigators noted that percent of body fat and the waist circumference were both inversely correlated with survival.

Dr. Meyerhardt and his group published an analysis of data from a National Cancer Institute–sponsored study called CALGB 89803 that involved 1,264 patients with stage II colon cancer, randomized to treatment with 5-fluorouracil and leucovorin with or without irinotecan following surgical resection.

The study was designed to assess the impact of the drug regimens on overall and disease-free survival, and found no significant differences between the two (J. Clin. Oncol. 2007;25:3456-61). However, there were substantial survival differences based on level of post-diagnosis physical activity, said Dr. Meyerhardt.

He and his colleagues stratified the study participants according to their self-reported activity levels, using the "met-hour" (metabolic equivalent task hour) as a unit of measure. For example, sitting still was defined as 1 met and slow walking was defined as 3 mets. Other activities were assigned met values according to their strenuousness. Met-hours represent the aggregate amount of time per week that a subject spent in metabolically significant activity.

The hazard ratio of recurrence or death was reduced by 49% among people who regularly had between 18 and 26 met-hours of activity per week, compared to those who had fewer than 3 met-hours per week (J. Clin. Oncol. 2006;24:3535-41). Dr. Meyerhardt said that an hour-long walk at a brisk pace of 3-4 miles per hour, three to four times per week, would put someone in the risk-reducing range.

He acknowledged that this analysis has limits in that it was based on self-reporting. Also, people who are able to exercise for 18 or more hours per week after chemotherapy and surgery for colorectal cancer are highly functioning, with good overall health status, which in and of itself would confer a survival advantage.

Data from other studies have also shown that higher activity levels predict better outcomes following colorectal cancer diagnosis. For example, the Nurses’ Health Study showed that post-diagnosis activity levels are predictive of survival. Among the women who had more than 18 met-hours of activity per week, roughly 90% were still alive 10 years after diagnosis, versus 67% of those who had less than 3 met hours per week, and 75% of those who got between 3 and 18 met-hours/week (J. Clin. Oncol. 2006;24:3527-34). In this data set, the prediagnosis activity levels were not predictive of survival, after researchers adjusted for other health status variables.

"It is not simply a matter of more active people getting less aggressive forms of cancer," said Dr. Meyerhardt. "There are statistically significant improvements in survival and reduced morbidity in patients with increased activity post-diagnosis and post-treatment."

The NHS data indicate that women who increased their activity levels post-diagnosis had about 50% reductions in hazard ratios for CRC-specific mortality and overall mortality, while those who decreased their physical activity had increases in their hazard ratios.

A soon-to-be published analysis of data from the Health Professionals Follow-Up Study, involving 51,500 male health care practitioners, showed a similar pattern of reduced overall and CRC-associated mortality among the men with the highest levels of post-diagnosis physical activity, said Dr. Meyerhardt.

He noted that these studies are observational, and a prospective study is needed to confirm their findings. The Colon Health and Life-Long Exercise Change (CHALLENGE) trial is such a study that is expected to be published in several years. An Australian-Canadian collaborative effort, this controlled study will look at the impact of direct, guided exercise training interventions on clinical outcomes in patients with high-risk stage II and III CRC following surgery and adjuvant chemotherapy.

It is not yet known how exercise affects CRC, and cancer in general. Dr. Meyerhardt believes that the potential benefits may be partially attributable to the ability of exercise to modulate insulin metabolism. He noted that elevated insulin and insulin-like growth factors are predictive of increased CRC morbidity and mortality, as is elevation of C-peptide, another marker of insulin resistance.

Insulin resistance and all the metabolic changes that go with it may be a common factor between obesity and colorectal cancer. While not all studies have shown a direct correlation, there are data to suggest that a BMI over 30 kg/m2confers a 25% increase in risk of colorectal cancer recurrence and death.

‘With the rising incidence of obesity in the U.S., we are seeing more obese colorectal cancer patients," said Dr. Meyerhardt. "It used to be that only about 5% of colorectal cancer patients were obese. Now it’s roughly 10%."

He concluded that while there are many unanswered questions, there’s little harm and much potential good in recommending moderate regular physical activity for patients who have undergone surgery and adjuvant chemotherapy for colorectal cancer. Benefits increase if patients can shift toward a low-fat diet rich in vegetables and low in red meat and processed foods, he added.